A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

Bell et al. report 46 new loci associated with biomarkers of iron homeostasis, including ferritin levels, iron binding capacity, and iron saturation, in the Icelandic, Danish and UK populations. The associated loci point to new iron-regulating proteins and important genetic differences between men and women

A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

Abstract: Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation

Migraine polygenic risk score associates with efficacy of migraine-specific drugs

Objective To assess whether the polygenic risk score (PRS) for migraine is associated with acute and/or prophylactic migraine treatment response. Methods We interviewed 2,219 unrelated patients at the Danish Headache Center using a semistructured interview to diagnose migraine and assess acute and prophylactic drug response. All patients were genotyped. A PRS was calculated with the linkage disequilibrium pred algorithm using summary statistics from the most recent migraine genome-wide association study comprising ∼375,000 cases and controls. The PRS was scaled to a unit corresponding to a twofold increase in migraine risk, using 929 unrelated Danish controls as reference. The association of the PRS with treatment response was assessed by logistic regression, and the predictive power of the model by area under the curve using a case-control design with treatment response as outcome. Results A twofold increase in migraine risk associates with positive response to migraine-specific acute treatment (odds ratio [OR] = 1.25 [95% confidence interval (CI) = 1.05–1.49]). The association between migraine risk and migraine-specific acute treatment was replicated in an independent cohort consisting of 5,616 triptan users with prescription history (OR = 3.20 [95% CI = 1.26–8.14]). No association was found for acute treatment with non–migraine-specific weak analgesics and prophylactic treatment response. Conclusions The migraine PRS can significantly identify subgroups of patients with a higher-than-average likelihood of a positive response to triptans, which provides a first step toward genetics-based precision medicine in migraine

Musculoskeletal pain, work posture and physical activity among professional symphony and opera musicians in Sweden

Godkänd; 2015; 20150530 (ulrroi

Occurrence and co-existence of localized musculoskeletal symptoms and findings in work-attending orchestra musicians - an exploratory cross-sectional study

Abstract Background Due to ergonomic exposure musicians are at risk of work-related musculoskeletal disorders in the neck, back, and upper extremities. The literature confirms musculoskeletal problems in these anatomic regions among orchestra musicians. Methods An explorative cross-sectional study among 441 musicians from six Danish symphony orchestras; 216 underwent a clinical examination constructed for the purpose. Prior to the examination the musicians rated their maximally perceived trouble within the last week on a scheme blinded to the examiner. Accessibility to the clinical examination differed between orchestras. The aims were to assess the prevalence of 1) perceived symptoms within the previous week in the neck, back and limbs and of 2) clinical findings in the neck, back, and upper extremities, and 3) to investigate the co-existence of the perceived symptoms and clinical findings. Results Symptoms and findings were most common in the neck, back, and shoulders. Due to a poor co-existence between self-reported symptoms and clinical findings musicians experiencing bodily trouble could not be identified through this clinical examination. Free accessibility to the examination was of major importance to participation. Conclusions In compliance with the purpose, perceived symptoms within the previous week and present clinical findings were assessed. Although both symptoms and findings were most frequent in the neck, back, and shoulders the co-existence of anatomically localized symptoms and findings was generally quite poor in this study. Discrepancy between symptoms and findings might be caused by the participants currently attending work and therefore being relatively healthy, and the fluctuating nature of musculoskeletal problems. Furthermore from a comparison of different measuring units - self-reported symptoms being period prevalence rates and clinical findings point prevalence rates; a bias which may also be inherent in similar studies combining self-reported questionnaire data and clinical findings.</p